There remains a critical need for medicines that can counteract the toxic effects of radiation exposure. Terapio is developing a recombinant protein, RLIP76, for use as a radioprotectant for workers, military personnel, or civilians that are either in imminent danger of radiation exposure, or have already been exposed. In research carried out at the University of Texas at Arlington, RLIP76 delivered in a liposome was discovered to have significant effects in protecting mice exposed to otherwise lethal doses of radiation, even if the proteoliposome was administered as late as 24 hours after exposure. Terapio was formed to develop and commercialize the protein for use as a radioprotectant. The company was awarded a Phase I SBIR from which exploratory efficacy studies were carried out confirming significant efficacy of the RLIP76 proteoliposome by a variety of routes of administration, including subcutaneous and intramuscular injection, a marked advantage for therapy that has to be delivered in the field. Now the company is applying for a Phase II SBIR to continue that work and carry out the studies necessary to file for an IND. Specifically, the goals of the current application are: 1.) to develop the necessary assays for IND-enabling studies and to verify the proposed tissue-level mechanism of action to the degree required by the FDA; 2.) to perform IND-enabling studies and 3.) to carry out animal safety and toxicokinetic studies in two species (rat and primate) as required by the FDA. Successful completion of these goals will position the company to file an IND in preparation for performing pivotal animal efficacy and human safety studies to support a subsequent New Drug Application. PUBLIC HEALTH RELEVANCE: The overall goal of this project is to carry out the studies necessary to allow RLIP76 protein to be successfully developed as a medicinal protectant against the toxicity of radiation exposure. Such a treatment will have enormous relevance to public health given the number of people in close proximity to nuclear facilities and the lack of current medical treatments for radiation toxicity.